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Find video protocols related to scientific articles indexed in Pubmed.
The efficacy of Botulinum Toxin A on improving ease of care in the upper and lower limbs: A systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach.
Clin Rehabil
PUBLISHED: 10-30-2014
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A systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach; evaluating Botulinum Toxin type A efficacy on improving ease of care in the upper/lower limb.
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Increased likelihood of mastectomy in human epidermal growth factor receptor 2-positive ductal carcinoma in situ.
Am Surg
PUBLISHED: 09-30-2014
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Patients with human epidermal growth factor receptor 2 (HER2neu)-positive breast invasive cancer are known to have larger, more aggressive tumors. Little research exists on the relationship between HER2neu status and extent of ductal carcinoma In Situ (DCIS). A retrospective review of a single-institution database was performed for patients with DCIS between the years 2002 and 2011. A single blinded breast radiologist reviewed preoperative imaging. Pathology was reviewed for extent of DCIS. Primary outcome was mastectomy. Multivariate logistic regression was used to determine adjusted mastectomy risk. There were 166 cases, 34 HER2neu-positive. HER2neu receptor-positive patients had larger lesions on imaging: 4.0 versus 2.7 cm, by 2.9 versus 1.5 cm (P = 0.0499 and 0.0182). HER2neu-positive patients with DCIS were more likely than HER2neu-negative to undergo mastectomy than lumpectomy (53 vs 28%, P = 0.006). Pathology revealed a trend toward larger lesions in HER2neu-positive patients (2.96 vs 2.22 cm, nonsignificant). Patients with HER2neu-positive disease were three times more likely to undergo mastectomy (odds ratio, 2.9; 95% confidence interval, 1.23 to 6.78). Patients with HER2neu-positive DCIS had greater extent of disease by imaging and were more likely to undergo mastectomy than HER2neu-negative. These findings will help surgeons counsel patients on surgical treatment.
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A Prospective Study of Height and Body Mass Index in Childhood, Birth Weight, and Risk of Adult Glioma Over 40 Years of Follow-up.
Am. J. Epidemiol.
PUBLISHED: 09-09-2014
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Greater attained height and greater body mass index (BMI; weight (kg)/height (m)(2)) in young adulthood have been associated with glioma risk, but few studies have investigated the association with body size at birth or during childhood, when the brain undergoes rapid cell growth and differentiation. The Copenhagen School Health Records Register includes data on 320,425 Danish schoolchildren born between 1930 and 1989, with height and weight measurements from ages 7-13 years and parentally recorded birth weights. We prospectively evaluated associations between childhood height and BMI, birth weight, and adult glioma risk. During follow-up (1968-2010), 355 men and 253 women aged ?18 years were diagnosed with glioma. In boys, height at each age between 7 and 13 years was positively associated with glioma risk; hazard ratios per standard-deviation score at ages 7 (approximately 5.1 cm) and 13 (approximately 7.6 cm) years were 1.17 (95% confidence interval (CI): 1.05, 1.30) and 1.21 (95% CI: 1.09, 1.35), respectively. No associations were observed for childhood height in girls or for BMI. Birth weight was positively associated with risk (per 0.5 kg: hazard ratio = 1.13, 95% CI: 1.04, 1.24). These results suggest that exposures associated with higher birth weight and, in boys, greater height during childhood may contribute to the etiology of adult glioma.
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"Warning signs" of primary immunodeficiency among patients with periprosthetic joint infection.
J Appl Biomater Funct Mater
PUBLISHED: 09-05-2014
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The use of ten clinical "warning signs" has been suggested as a screening tool to identify patients that may have primary immunodeficiency (PID) conditions in adulthood. This study aimed to evaluate the presence of these "warning signs" among a cohort of patients with periprosthetic joint infections (PJI), in order to detect those cases that may have had a PID contributing to development of infection.
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Adipose-derived stem cells: methods for isolation and applications for clinical use.
Methods Mol. Biol.
PUBLISHED: 09-01-2014
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Adipose tissue sciences have rapidly expanded since the identification of regenerative cells contained within the stromal vascular fraction (SVF) of fat. Isolation of the SVF, containing adipose-derived stem cells (ADSC), can be accomplished efficiently in the operating room or in the laboratory through enzymatic digestion of the adipose tissue and concentration of SVF. Cells can be directly re-injected as a mesotherapeutic agent, recombined with a tissue scaffold (e.g., cell-enriched fat grafts) or expanded in culture for tissue-engineered cell therapeutics. The potential for cell therapy is under current investigation by researchers around the world. This chapter reviews laboratory methods for isolating ADSCs and the ongoing clinical trials evaluating cell therapeutic efficacy across many specialties, including cardiology, neurology, immunology, tissue engineering, sports medicine, and plastic and reconstructive surgery.
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Tissue penetration and activity of camptothecins in solid tumor xenografts.
Mol. Cancer Ther.
PUBLISHED: 08-20-2014
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The ability of a panel of camptothecin derivatives to access the tumor compartment was evaluated to determine the mechanisms by which the architecture of solid tumors may act to limit their activity. Microregional localization and activity of members of the camptothecin class of topoisomerase I targeting agents, including topotecan, irinotecan, and irinophore C, a lipid-based nanoparticulate formulation of irinotecan, were evaluated over time in HCT116 and HT29 colorectal tumor xenografts. Using native drug fluorescence, their distributions in tissue cryosections were related to the underlying tumor vasculature, tumor cell proliferation, and apoptosis. Topotecan exhibited a relatively uniform tumor distribution; in tissue 100 ?m away from vessels, it reached 94% ± 5% of levels seen around blood vessels, whereas irinotecan and irinophore C were found to reach only 41% ± 10% and 5% ± 2%, respectively. Surprisingly, all three agents were able to initially inhibit proliferation uniformly throughout the tumors, and it was their rate of washout (topotecan > irinotecan > irinophore C) that correlated with activity. To explain this discrepancy, we looked at SN38, the active metabolite of irinotecan, and found it to penetrate tissue similarly to topotecan. Hence, the poor access to the tumor compartment of irinotecan and irinophore C could be offset by their systemic conversion to SN38. It was concluded that all three agents were effective at reaching tumor cells, and that despite the poor access to the extravascular compartment of irinophore C, its extended plasma exposure and systemic conversion to the diffusible metabolite SN38 enabled it to effectively target solid tumors. Mol Cancer Ther; 13(11); 2727-37. ©2014 AACR.
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Risperidone added to parent training and stimulant medication: effects on attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression.
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 06-12-2014
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In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication, and placebo (Basic therapy) versus parent training, stimulant, and risperidone (Augmented therapy) by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced impairment, and informant discrepancy.
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Comparison of [(99m)Tc]Tilmanocept and Filtered [(99m)Tc]Sulfur Colloid for Identification of SLNs in Breast Cancer Patients.
Ann. Surg. Oncol.
PUBLISHED: 04-22-2014
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The efficacy of sentinel lymph node (SLN) surgery requires targeted removal of first-draining nodes; however, frequently more nodes are removed than necessary. [(99m)Tc]tilmanocept (TcTM) is a molecular-targeted radiopharmaceutical specifically designed for SLN mapping. We evaluated technical outcomes of SLN biopsy in breast cancer patients mapped with TcTM + vital blue dye (VBD) versus filtered [(99m)Tc]sulfur colloid (fTcSC) + VBD.
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Designing a resident research program.
Am J Health Syst Pharm
PUBLISHED: 03-20-2014
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The development of a resident research program and the role of the residency research advisory board (RRAB) in the program are described.
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Endothelial-specific Notch blockade inhibits vascular function and tumor growth through an eNOS-dependent mechanism.
Cancer Res.
PUBLISHED: 03-05-2014
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Notch signaling is important for tumor angiogenesis induced by vascular endothelial growth factor A. Blockade of the Notch ligand Dll4 inhibits tumor growth in a paradoxical way. Dll4 inhibition increases endothelial cell sprouting, but vessels show reduced perfusion. The reason for this lack of perfusion is not currently understood. Here we report that inhibition of Notch signaling in endothelial cell using an inducible binary transgenic system limits VEGFA-driven tumor growth and causes endothelial dysfunction. Neither excessive endothelial cell sprouting nor defects of pericyte abundance accompanied the inhibition of tumor growth and functional vasculature. However, biochemical and functional analysis revealed that endothelial nitric oxide production is decreased by Notch inhibition. Treatment with the soluble guanylate cyclase activator BAY41-2272, a vasorelaxing agent that acts downstream of endothelial nitric oxide synthase (eNOS) by directly activating its soluble guanylyl cyclase receptor, rescued blood vessel function and tumor growth. We show that reduction in nitric oxide signaling is an early alteration induced by Notch inhibition and suggest that lack of functional vessels observed with Notch inhibition is secondary to inhibition of nitric oxide signaling. Coculture and tumor growth assays reveal that Notch-mediated nitric oxide production in endothelial cell requires VEGFA signaling. Together, our data support that eNOS inhibition is responsible for the tumor growth and vascular function defects induced by endothelial Notch inhibition. This study uncovers a novel mechanism of nitric oxide production in endothelial cells in tumors, with implications for understanding the peculiar character of tumor blood vessels.
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Birth weight, childhood body mass index, and height in relation to mammographic density and breast cancer: a register-based cohort study.
Breast Cancer Res.
PUBLISHED: 01-06-2014
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High breast density, a strong predictor of breast cancer may be determined early in life. Childhood anthropometric factors have been related to breast cancer and breast density, but rarely simultaneously. We examined whether mammographic density (MD) mediates an association of birth weight, childhood body mass index (BMI), and height with the risk of breast cancer.
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Fluorescent-tilmanocept for tumor margin analysis in the mouse model.
J. Surg. Res.
PUBLISHED: 01-03-2014
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Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment.
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Trends in Parent-Child Correlations of Childhood Body Mass Index during the Development of the Obesity Epidemic.
PLoS ONE
PUBLISHED: 01-01-2014
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The intergenerational resemblance in body mass index may have increased during the development of the obesity epidemic due to changes in environment and/or expression of genetic predisposition.
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Childhood Height and Body Mass Index Were Associated with Risk of Adult Thyroid Cancer in a Large Cohort Study.
Cancer Res.
PUBLISHED: 11-18-2013
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Taller stature and obesity in adulthood have been consistently associated with an increased risk of thyroid cancer, but few studies have investigated the role of childhood body size. Using data from a large prospective cohort, we examined associations for height and body mass index (BMI) at ages 7 to 13 years with risk of thyroid cancer in later life. The study population included 321,085 children from the Copenhagen School Health Records Register, born between 1930 and 1989 in Copenhagen, Denmark, with measurements of height and weight from 7 to 13 years of age. These data were linked with the Danish Cancer Registry to identify incident thyroid cancer cases (1968-2010). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for age- and sex-specific height and BMI SD scores (SDS) using proportional hazards models stratified by birth cohort and sex. During follow-up (median = 38.6 years), 171 women and 64 men were diagnosed with thyroid cancer. Both height and BMI were positively associated with thyroid cancer risk, and these associations were similar by age at measurement. Using age 10 as an example, HRs per 1 unit increase in SDS for height (?6-7 cm) and BMI (? 1.5-2 kg/m(2)) were 1.22 (95% CI, 1.07-1.40) and 1.15 (95% CI, 1.00-1.34), respectively. These results, together with the relatively young ages at which thyroid cancers are diagnosed compared with other malignancies, suggest a potential link between early-life factors related to growth and body weight and thyroid carcinogenesis. Cancer Res; 74(1); 1-8. ©2013 AACR.
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Postmastectomy reconstruction is associated with improved survival in patients with invasive breast cancer: a single-institution study.
Am Surg
PUBLISHED: 10-29-2013
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Breast reconstruction after mastectomy positively affects psychosocial well-being; however, the influence of reconstruction on cancer outcomes is unknown. The objective of our study was to compare survival in reconstructed versus nonreconstructed patients after mastectomy. All consecutive female patients diagnosed with invasive breast cancer and treated with mastectomy between 2002 and 2011 were identified from our single-institution database. All cancer operations were performed by two surgeons. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. To identify the effect of reconstruction on survival, a multivariate Cox regression analysis was performed. Of 474 patients treated, 340 (71.7%) underwent breast reconstruction. At a mean follow-up 3.3 years, reconstructed patients had a longer 5-year survival (91 vs 74%, P < 0.001). After controlling for age, race, payer source, cancer stage, triple negative status, and receipt of radiation or chemotherapy, reconstructed patients maintained a survival advantage over nonreconstructed patients (hazard ratio, 0.47; 95% confidence interval, 0.25 to 0.88; P = 0.02). Patients with breast cancer who undergo reconstruction have longer survival than nonreconstructed patients. The explanation for this finding may be related to improved psychosocial qualities of life versus possible antitumorigenic effects of implants.
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Childhood height and birth weight in relation to future prostate cancer risk: a cohort study based on the copenhagen school health records register.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-02-2013
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Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR).
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The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach.
Clin Rehabil
PUBLISHED: 07-17-2013
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A systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to evaluate Botulinum Toxin Type A efficacy on spasticity and pain in the upper/lower limb in adults.
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What does risperidone add to parent training and stimulant for severe aggression in child attention-deficit/hyperactivity disorder?
J Am Acad Child Adolesc Psychiatry
PUBLISHED: 05-16-2013
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Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested.
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Body mass index in childhood and adult risk of primary liver cancer.
J. Hepatol.
PUBLISHED: 05-03-2013
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Childhood overweight increases the risk of early development of non-alcoholic fatty liver disease, which may predispose to carcinogenesis. We investigated if childhood body size during school ages was associated with the risk of primary liver cancer in adults.
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Childhood body mass index and multiple sclerosis risk: a long-term cohort study.
Mult. Scler.
PUBLISHED: 04-02-2013
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Obesity in late adolescence has been associated with an increased risk of multiple sclerosis (MS); however, it is not known if body size in childhood is associated with MS risk.
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A Comparison of Cell-Enriched Fat Transfer to Conventional Fat Grafting after Aesthetic Procedures Using a Patient Satisfaction Survey.
Ann Plast Surg
PUBLISHED: 03-15-2013
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INTRODUCTION: The role of regenerative cells in adult human fat is still unfolding. At present, limited clinical studies comparing patient satisfaction with cell-enriched fat transfer (CEFT) to conventional autologous fat transfer (AFT) for aesthetic indications have been performed. Herein, we present our data obtained from patient satisfaction questionnaires. METHODS: Patients undergoing fat grafting received AFT or CEFT. Study participants were surveyed for overall satisfaction, symmetry, deformity, scarring, and pigmentation. Hospital charts were reviewed for complications, and patient survey responses between the groups were compared. RESULTS: Between January 2009 and September 2011, 36 patients had 6-months follow-up and were mailed surveys. Of these, 17 (12 CEFT and 5 AFT) returned completed Patient Satisfaction Rating surveys. At a median follow-up time of 10.7 months, the overall mean satisfaction rate was 5.2 of 6 (5.3 vs 5.0 for CEFT and AFT, respectively, P = 0.42). There were no significant differences about deformity (5.1 vs 4.7, P = 0.50), symmetry (4.5 vs 5.0, P = 0.48), or scarring (5.3 vs 4.5, P = 0.23). However, pigmentation was improved in the CEFT vs the AFT groups (P < 0.001). No patients in the AFT group noted skin pigmentation improvement, whereas 7 of 12 receiving CEFT noted improvement in skin pigmentation. CONCLUSIONS: Cell-enriched fat transfer to the face and body of aesthetic patients produces high satisfaction rates. Our preliminary data demonstrates similar satisfaction with regard to symmetry, scarring, and deformity in patients treated with CEFT versus AFT, without any complications. Unexpectedly, a clinical and statistical improvement in pigmentation was seen for patients treated with CEFT over AFT. Further studies need to be done to better understand this phenomenon.
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Targeting the Tumour Vasculature: Exploitation of Low Oxygenation and Sensitivity to NOS Inhibition by Treatment with a Hypoxic Cytotoxin.
PLoS ONE
PUBLISHED: 01-01-2013
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Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ) mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels.
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Targeting quiescent tumor cells via oxygen and IGF-I supplementation.
Cancer Res.
PUBLISHED: 12-12-2011
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Conventional chemotherapy targets proliferating cancer cells, but most cells in solid tumors are not in a proliferative state. Thus, strategies to enable conventional chemotherapy to target noncycling cells may greatly increase tumor responsiveness. In this study, we used a 3-dimensional tissue culture system to assay diffusible factors that can limit proliferation in the context of the tumor microenvironment, with the goal of identifying targets to heighten proliferative capacity in this setting. We found that supraphysiologic levels of insulin or insulin-like growth factor I (IGF-I) in combination with oxygen supplementation were sufficient to initiate proliferation of quiescence cells in this system. At maximal induction with IGF-I, net tissue proliferation increased 3- to 4-fold in the system such that chemotherapy could trigger a 3- to 6-fold increase in cytotoxicity, compared with control conditions. These effects were confirmed in vivo in colon cancer xenograft models with demonstrations that IGF-I receptor stimulation was sufficient to generate a 45% increase in tumor cell proliferation, along with a 25% to 50% increase in chemotherapy-induced tumor growth delay. Although oxygen was a dominant factor limiting in vitro tumor cell proliferation, we found that oxygen supplementation via pure oxygen breathing at 1 or 2 atmospheres pressure (mimicking hyperbaric therapy) did not decrease hypoxia in the tumor xenograft mouse model and was insufficient to increase tumor proliferation. Thus, our findings pointed to IGF-I receptor stimulation as a rational strategy to successfully increase tumor responsiveness to cytotoxic chemotherapy.
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Tissue uptake of docetaxel loaded hydrophobically derivatized hyperbranched polyglycerols and their effects on the morphology of the bladder urothelium.
Biomaterials
PUBLISHED: 09-09-2011
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Recently, we have reported that docetaxel (DTX) loaded, amine terminated hyperbranched polyglycerol (HPG-C(8/10)-MePEG-NH(2)) nanoparticles significantly increased drug uptake in mouse bladder tissues and was the most effective formulation to significantly inhibit tumor growth in an orthotopic model of bladder cancer. The objective of this study was to investigate the effects of HPG-C(8/10)-MePEG-NH(2) nanoparticles on bladder urothelial morphology and integrity, DTX uptake and permeability in bladder tissue and the extent of bladder urothelial recovery following exposure to, and then washout of, HPG-C(8/10)-MePEG-NH(2) nanoparticles. HPG-C(8/10)-MePEG-NH(2) nanoparticles significantly increased the uptake of DTX in both isolated pig bladder as well as in live mouse bladder tissues. Furthermore, HPG-C(8/10)-MePEG-NH(2) nanoparticles were demonstrated to increase the permeability of the urinary bladder wall by causing changes to the urothelial barrier function and morphology through opening of tight junctions and exfoliation of the superficial umbrella cells. These data suggest that exfoliation may be triggered by an apoptosis mechanism, which was followed by a rapid recovery of the urothelium within 24 h post-instillation of HPG-C(8/10)-MePEG-NH(2) nanoparticles. HPG-C(8/10)-MePEG-NH(2) nanoparticles cause significant but rapidly recoverable changes in the bladder urothelial morphology, which we believe may make them suitable for increasing drug permeability of bladder tissue and intravesical drug delivery.
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Obesity research based on the Copenhagen School Health Records Register.
Scand J Public Health
PUBLISHED: 07-22-2011
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To summarise key findings from research performed using data from the Copenhagen School Health Records Register over the last 30 years with a main focus on obesity-related research. The register contains computerised anthropometric information on 372,636 schoolchildren from the capital city of Denmark. Additional information on the cohort members has been obtained via linkages with population studies and national registers.
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The Copenhagen School Health Records Register.
Scand J Public Health
PUBLISHED: 07-22-2011
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The Copenhagen School Health Records Register is an electronic register of health examination information on 372,636 children who attended school in Copenhagen, Denmark from 1936 to 2005.
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The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing breast cancer cells and tumors irrespective of trastuzumab sensitivity.
BMC Cancer
PUBLISHED: 07-06-2011
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HER2-positive breast cancers exhibit high rates of innate and acquired resistance to trastuzumab (TZ), a HER2-directed antibody used as a first line treatment for this disease. TZ resistance may in part be mediated by frequent co-expression of EGFR and by sustained activation of the mammalian target of rapamycin (mTOR) pathway. Here, we assessed feasibility of combining the EGFR inhibitor gefitinib and the mTOR inhibitor everolimus (RAD001) for treating HER2 overexpressing breast cancers with different sensitivity to TZ.
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Reduced tumour progression and angiogenesis in 1,2-dimethylhydrazine mice treated with NS-398 is associated with down-regulation of cyclooxygenase-2 and decreased beta-catenin nuclear localisation.
Cell Commun. Adhes.
PUBLISHED: 06-16-2011
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Cyclooxygenase (COX)-2 is a key molecular target of colon cancer prevention. However, the mechanisms by which COX-2 inhibitors confer protective effects against tumour development are not completely understood. The aim of this study was to elucidate the effects of NS-398 in the 1,2-dimethylhydrazine (DMH) mouse model with respect to alteration in the expression of COX-2 and E-cadherin-catenin complex. Alterations in cell proliferation, apoptosis, and vascular density were investigated. NS-398 showed reduced COX-2 immunoreactivity in adenomas with a decrease in vascular density in non-dysplastic mucosa. Adenomas revealed increased E-cadherin and beta-catenin reactivity. NS-398 reduced the percentages of tumour cells with nuclear localisation of beta-catenin and cyclin D1. Bromodeoxyuridine (BrdUrd) index in adenomas was significantly higher in untreated animals. NS-398 resulted in significant increase in apoptosis in adenomas. Our results suggest a protective role of NS-398 on tumour development associated with reduced COX-2 expression, reduced vascular density and perturbation of beta-catenin signalling pathway.
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Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Science
PUBLISHED: 04-07-2011
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Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an essential negative regulator of T cell immune responses whose mechanism of action is the subject of debate. CTLA-4 shares two ligands (CD80 and CD86) with a stimulatory receptor, CD28. Here, we show that CTLA-4 can capture its ligands from opposing cells by a process of trans-endocytosis. After removal, these costimulatory ligands are degraded inside CTLA-4-expressing cells, resulting in impaired costimulation via CD28. Acquisition of CD86 from antigen-presenting cells is stimulated by T cell receptor engagement and observed in vitro and in vivo. These data reveal a mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by the cell-extrinsic depletion of ligands, accounting for many of the known features of the CD28-CTLA-4 system.
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In vivo evaluation of mucoadhesive nanoparticulate docetaxel for intravesical treatment of non-muscle-invasive bladder cancer.
Clin. Cancer Res.
PUBLISHED: 02-28-2011
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The present work describes the development and in vitro and in vivo evaluation of a mucoadhesive nanoparticulate docetaxel (DTX) formulation for intravesical bladder cancer therapy.
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INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.
J Manag Care Pharm
PUBLISHED: 02-26-2011
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In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care.
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Birthweight and mortality in adulthood: a systematic review and meta-analysis.
Int J Epidemiol
PUBLISHED: 02-15-2011
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Small birth size may be associated with increased risk of cardiovascular diseases (CVD), whereas large birth size may predict increased risk of obesity and some cancers. The net effect of birth size on long-term mortality has only been assessed in individual studies, with conflicting results.
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Opposing roles for CD34 in B16 melanoma tumor growth alter early stage vasculature and late stage immune cell infiltration.
PLoS ONE
PUBLISHED: 01-04-2011
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Tumor growth and metastasis are determined by the complex interplay of factors, including those intrinsic to tumor cells and extrinsic factors associated with the tumor microenvironment. Our previous work demonstrated key roles for CD34 in the maintenance of vascular integrity and eosinophil and mast cell homing. Since both of these functions affect tumor development, we characterized the effect of CD34 ablation on tumor growth using the B16F1 melanoma model. Intriguingly, we found that CD34 plays a biphasic role in tumor progression. In early growth, both subcutaneous-injected tumors and intravenous-injected lung metastases grew more slowly in Cd34(-/-) mice. This correlated with abnormal vessel morphology and increased vascular permeability in these mice. Bone marrow transplantation experiments confirmed that this reflects a non-hematopoietic function of CD34. At later stages, subcutaneous tumor growth was accelerated in Cd34(-/-) mice and surpassed growth in wildtype mice. Bone marrow chimera experiments demonstrated this difference was due to a hematopoietic function for CD34 and, correspondingly we found reduced intra-tumor mast cell numbers in Cd34(-/-) mice. In aggregate, our analysis reveals a novel role for CD34 in both early and late tumor growth and provides novel insights into the role of the tumor microenvironment in tumor progression.
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High body mass index in adolescent girls precedes psoriasis hospitalization.
Acta Derm. Venereol.
PUBLISHED: 09-04-2010
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Psoriasis is associated with being overweight, but the temporal relationship is not known. This historical cohort study tested whether severe psoriasis resulting in hospitalization in adulthood was preceded by excess increase in age-adjusted body mass index, a known risk factor in childhood for being overweight in adulthood. The study cohort was based on the Copenhagen School Health Records Register, birth years 1930 to 1984 (309,152 schoolchildren). Cases were found through the Danish National Patient Register for the period 1977 to 2001. A total of 1074 (0.36%) of the schoolchildren were identified as having psoriasis, with at least one hospital admission. Multivariate analysis demonstrated an association between excess increase in body mass index and psoriasis in females only. Being overweight in adolescence was the main factor behind this observation. The female group showed a significant association between psoriasis and body mass index at ages 12 (p = 0.028) and 13 years (p = 0.010). This was not the case for males or for body mass index measured at ages 11 years and below.
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Influence of psychosocial factors on postpartum weight retention.
Obesity (Silver Spring)
PUBLISHED: 08-12-2010
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For some women, pregnancy may increase the risk of future obesity with consequences for health and well-being. Psychosocial factors may be partly responsible for this. The aim of this study was to examine the association between psychosocial factors during pregnancy and postpartum weight retention (PPWR) at 6 and 18 months. A total of 37,127 women in The Danish National Birth Cohort (DNBC; 1996-2002) participated in four telephone interviews before and after delivery. They gave information about their experience of distress, depression and anxiety, social support, and psychosocial burdens during pregnancy. PPWR was defined as retention ? 5 kg at 6 and 18 months postpartum according to a womans prepregnancy weight. The associations were examined by use of logistic regression and presented as odds radios with 95% confidence intervals. Women who were more likely to feel depressed/anxious or distressed during pregnancy had a higher risk of PPWR at 6 months (1.35 (1.27; 1.44) and 1.30 (1.22; 1.38)) and 18 months (1.34 (1.24; 1.45) and 1.32 (1.23; 1.42)). Likewise, women who felt burdened by their economy or working situation had a higher risk of PPWR as did women with the lowest incomes or less education. Women who reported a high level of distress or depression/anxiety both during pregnancy and in the first 6 months of motherhood had the highest risk of PPWR 18 months postpartum (1.54 (1.39; 1.71) and 1.49 (1.32; 1.69), respectively). Feeling distressed, depressed, or anxious during pregnancy was associated with higher PPWR as was personal and economical burdens. Adverse psychosocial characteristics may be a common determinant of weight retention after childbirth.
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Birth weight, childhood body mass index and risk of coronary heart disease in adults: combined historical cohort studies.
PLoS ONE
PUBLISHED: 07-20-2010
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Low birth weight and high childhood body mass index (BMI) is each associated with an increased risk of coronary heart disease (CHD) in adult life. We studied individual and combined associations of birth weight and childhood BMI with the risk of CHD in adulthood.
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Overweight and obesity trends in Copenhagen schoolchildren from 2002 to 2007.
Acta Paediatr.
PUBLISHED: 06-14-2010
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The purpose of this study is to monitor the prevalence trend in overweight and obesity among Copenhagen schoolchildren from the school years 2002 to 2007.
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Prenatal stress exposure related to maternal bereavement and risk of childhood overweight.
PLoS ONE
PUBLISHED: 04-06-2010
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It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population-based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.
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Evaluation of the overweight/obese child--practical tips for the primary health care provider: recommendations from the Childhood Obesity Task Force of the European Association for the Study of Obesity.
Obes Facts
PUBLISHED: 04-06-2010
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The prevalence of obesity among children and adolescents is on the rise. The majority of overweight or obese children are treated by primary health care providers including paediatricians, family practitioners, dieticians, nurses, and school health services - and not by specialists. The majority of obese children have no underlying medical disorder causing their obesity yet a significant proportion might suffer from obesity-related co-morbidities. This text is aimed at providing simple and practical tools for the identification and management of children with or at risk of overweight and obesity in the primary care setting. The tips and tools provided are based on data from the recent body of work that has been published in this field, official statements of several scientific societies along with expert opinion provided by the members of the Childhood Obesity Task Force (COTF) of the European Association for the Study of Obesity (EASO). We have attempted to use an evidence-based approach while allowing flexibility for the practicing clinician in domains where evidence is currently lacking and ensuring that treating the obese child involves the entire family as well.
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Interactions between buprenorphine and antiretrovirals: nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine, lamivudine, and tenofovir.
Am J Addict
PUBLISHED: 02-06-2010
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To improve outcomes among injection drug users with HIV and/or chronic hepatitis B, it is important to identify drug interactions between antiretroviral and opiate therapies. We report the results of a study designed to examine the interaction between buprenorphine and the nucleos(t)ide reverse transcriptase inhibitors (NRTI) didanosine (ddI), lamivudine (3TC), and tenofovir (TDF). Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 27) participated in two 24-hour sessions to determine (1) pharmacokinetics of buprenorphine alone and (2) pharmacokinetics of both buprenorphine and either ddI, 3TC, or TDF. Among buprenorphine/naloxone-maintained study participants, no significant changes in buprenorphine pharmacokinetics were observed following ddI, 3TC, or TDF administration. Buprenorphine had no significant effect on NRTI concentrations. Concomitant use of buprenorphine with ddI, 3TC, or TDF results in neither a significant pharmacokinetic nor pharmacodynamic interaction.
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Pregnancy outcomes related to gestational weight gain in women defined by their body mass index, parity, height, and smoking status.
Am. J. Clin. Nutr.
PUBLISHED: 09-16-2009
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Recommendations for gestational weight gain (GWG) account for a womans prepregnancy body mass index (BMI), but other factors may be important.
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Risk of lymphoma and leukaemia after bacille Calmette-Guérin and smallpox vaccination: a Danish case-cohort study.
Vaccine
PUBLISHED: 07-23-2009
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Vaccines may have non-specific effects as suggested mainly in mortality studies from low-income countries. The objective was to examine the effects of BCG and smallpox vaccinations on subsequent risk of lymphoma and leukaemia in a Danish population experiencing rapid out-phasing of these vaccines. In a background cohort (N=47,622) from the Copenhagen School Health Records Register, cases of leukaemia (N=20) and lymphoma (N=51) were identified through the Danish Cancer Registry. The vaccination status of the cases was compared with the vaccination status of a 5% random sample (N=2073) of the background cohort and analysed in a case-cohort design. BCG vaccination reduced the risk of lymphomas (HR=0.49 (95% CI: 0.26-0.93)), whereas smallpox vaccination did not (HR=1.32 (0.56-3.08)). With the small number of leukaemia cases, the analysis of leukaemia had limited power (BCG vaccination HR=0.81 (0.31-2.16); smallpox vaccination HR=1.32 (0.49-3.53)). The present study with very reliable vaccine history information indicates a beneficial effect of BCG vaccination on the risk of lymphomas.
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Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts.
PLoS ONE
PUBLISHED: 07-20-2009
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Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk.
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Baseline articular contact stress levels predict incident symptomatic knee osteoarthritis development in the MOST cohort.
J. Orthop. Res.
PUBLISHED: 06-18-2009
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We studied whether contact stress estimates from knee magnetic resonance images (MRI) predict the development of incident symptomatic tibiofemoral osteoarthritis (OA) 15 months later in an at-risk cohort. This nested case-control study was conducted within a cohort of 3,026 adults, age 50 to 79 years. Thirty cases with incident symptomatic tibiofemoral OA by their 15 month follow-up visit were randomly selected and matched with 30 control subjects. Symptomatic tibiofemoral OA was defined as daily knee pain/stiffness and Kellgren-Lawrence Grade > or =2 on weight bearing, fixed-flexion radiographs. Tibiofemoral geometry was segmented on baseline knee MRI, and contact stresses were estimated using discrete element analysis. Linear mixed models for repeated measures were used to examine the association between articular contact stress and case/control status. No significant intergroup differences were found for age, sex, BMI, weight, height, or limb alignment. However, the maximum articular contact stress was 0.54 +/- 0.77 MPa (mean +/- SD) higher in incident OA cases compared to that in control knees (p = 0.0007). The interaction between case-control status and contact stress was significant above 3.20 MPa (p < 0.0001). The presence of differences in estimated contact stress 15 months prior to incidence suggests a biomechanical mechanism for symptomatic tibiofemoral OA and supports the ability to identify risk by subject-specific biomechanical modeling.
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Detecting vascular-targeting effects of the hypoxic cytotoxin tirapazamine in tumor xenografts using magnetic resonance imaging.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 06-02-2009
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To determine whether vascular-targeting effects can be detected in vivo using magnetic resonance imaging (MRI).
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Life course path analysis of birth weight, childhood growth, and adult systolic blood pressure.
Am. J. Epidemiol.
PUBLISHED: 04-08-2009
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The inverse associations between birth weight and later adverse health outcomes and the positive associations between adult body size and poor health imply that increases in relative body size between birth and adulthood may be undesirable. In this paper, the authors describe life course path analysis, a method that can be used to jointly estimate associations between body sizes at different time points and associations of body sizes throughout life with health outcomes. Additionally, this method makes it possible to assess both the direct effect and the indirect effect mediated through later body size, and thereby the total effect, of size and changes in size on later outcomes. Using data on childhood body size and adult systolic blood pressure from a sample of 1,284 Danish men born between 1936 and 1970, the authors compared results from path analysis with results from 3 standard regression methods. Path analysis produced easily interpretable results, and compared with standard regression methods it produced a noteworthy gain in statistical power. The effect of change in relative body size on adult blood pressure was more pronounced after age 11 years than in earlier childhood. These results suggest that increases in body size prior to age 11 years are less harmful to adult blood pressure than increases occurring after this age.
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Correcting for fat mass improves DXA quantification of quadriceps specific strength in obese adults aged 50-59 years.
J Clin Densitom
PUBLISHED: 01-01-2009
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Dual-energy X-ray absorptiometry (DXA) is widely used for bone mineral density and body composition assessments. However, DXA is known to overestimate muscle mass in obese adults. We used single-slice CT (ssCT) to derive a correction factor to enhance accuracy of DXA estimation of specific strength (strength per unit muscle). One hundred and sixty-two adults (age: 55.0+/-2.7 yr, range: 50-59) were enrolled in this cross-sectional study and divided into groups based on body mass index (BMI: <30, 30-35, and > or =35). BMI groups did not differ in age, knee extensor strength (KES), thigh lean mass by DXA, or quadriceps cross-sectional area (CSA) by ssCT. Specific strength (KES/CSA) correlated with an uncorrected estimate of DXA-specific strength (r = 0.82, 0.53, 0.84 and 0.74, 0.59, 0.57, p < 0.001) in the lowest to highest BMI groups in men and women, respectively. Stronger correlations were achieved through correcting for BMI, age, and sex in estimating DXA-specific strength (r = 0.81, 0.79, and 0.96 in the lowest to highest BMI groups in men and 0.94, 0.81, 0.85 in women, p < 0.0001). Quantification of knee extensor-specific strength by DXA in men with BMI > 30 and all BMI groups in women greatly improved using a correction factor for DXA estimates of thigh lean mass.
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Atypical Ductal Hyperplasia at the Margin of Lumpectomy Performed for Early Stage Breast Cancer: Is there Enough Evidence to Formulate Guidelines?
Int J Surg Oncol
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Background. Negative margins are associated with a reduced risk of ipsilateral breast tumor recurrence (IBTR) in women with early stage breast cancer treated with breast conserving surgery (BCS). Not infrequently, atypical ductal hyperplasia (ADH) is reported as involving the margin of a BCS specimen, and there is no consensus among surgeons or pathologists on how to approach this diagnosis resulting in varied reexcision practices among breast surgeons. The purpose of this paper is to establish a reasonable approach to guide the treatment of ADH involving the margin after BCS for early stage breast cancer. Methods. the published literature was reviewed using the PubMed site from the US National Library of Medicine. Conclusions. ADH at the margin of a BCS specimen performed for early stage breast cancer is a controversial pathological diagnosis subject to large interobserver variability. There is not enough data evaluating this diagnosis to change current practice patterns; however, it is reasonable to consider reexcision for ADH involving a surgical margin, especially if it coexists with low grade DCIS. Further studies with longer followup and closer attention to ADH at the margin are needed to formulate treatment guidelines.
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Bereavement in early life and later childhood overweight.
Obes Facts
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The rise in the occurrence of childhood obesity during the last decades in many populations indicates an important role of environmental exposures, which may operate very early in life. We aimed to examine the association between bereavement during the first 6 years of life, as a stress indicator, and subsequent risk of overweight in school-aged children.
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Development of obesity and polycystic ovary syndrome in adolescents.
Horm Res Paediatr
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Obesity in adolescents is prevalent worldwide. Polycystic ovary syndrome (PCOS) is often associated with obesity in women, and it has serious metabolic and reproductive health implications. Although PCOS does not become clinically visible until early adolescence, its origins are likely much earlier. Therefore, we reviewed the recent literature regarding the mechanisms linking the development of PCOS and obesity in adolescent girls. We found that excess abdominal adipose tissue (AT) initiates metabolic and endocrine aberrations that are central in the progression of PCOS. As an example, abdominal AT impairs insulin action, which interacts with the progression of hyperandrogenism. In addition, excessive androgen levels lead to impaired glucose uptake, which also contributes to insulin resistance, which again increases the deposition of visceral fat. The body composition is influenced by testosterone, which decreases subcutaneous fat lipolysis and influences adipocyte distribution. These mechanisms may explain why PCOS girls have an increased visceral adipose mass independent of body mass index. Therefore, first-line treatment in adolescent PCOS is often lifestyle intervention to prevent the damaging effects of obesity. Pharmacological treatment of adolescent PCOS is not standardized because the long-term effects in adolescents have not yet been evaluated; therefore, drugs should be prescribed cautiously. Although the complex metabolic interrelationships between obesity and PCOS have yet to be fully understood, the co-occurrence of these conditions in adolescent girls tends to increase the severity of the negative health consequences of each condition.
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Assortative marriages by body mass index have increased simultaneously with the obesity epidemic.
Front Genet
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Background: The genetic predisposition to obesity may have contributed to the obesity epidemic through assortative mating. We investigated whether spouses were positively assorted by body mass index (BMI; = kg/m(2)) in late childhood, and whether changes in assorted marriage by upper BMI-percentiles occurred during the obesity epidemic. Methods: In the Copenhagen School Health Records Register (CSHRR) boys and girls with measures of BMI at age 13 years later became 37,792 spousal-pairs who married between 1945 and 2010. Trends in the spousal BMI correlations using sex-, age-, and birth cohort-specific BMI z-scores across time were investigated. Odds ratios (ORs) of marriage among spouses both with BMI z-scores >90th or >95th percentile compared with marriage among spouses ?90th percentile were analyzed for marriages entered during the years prior to (1945-1970), and during the obesity epidemic (1971-2010). Findings: Spousal BMI correlations were around 0.05 and stayed similar across time. ORs of marriage among spouses with BMIs >90th percentile at age 13 were 1.21, 1.05-1.39, in 1945-1970, and increased to 1.63, 1.40-1.91, in 1971-2010 (p = 0.006). ORs of marriage among spouses both >95th BMI percentile were higher and increased more; from 1.39, 1.10-1.81, to 2.39, 1.85-3.09 (p = 0.004). Interpretation: Spousal correlations by pre-marital BMIs were small and stable during the past 65 years. Yet, there were assorted marriages between spouses with high BMI at age 13 years and the tendency increased alongside with the obesity epidemic which may increase the offsprings predisposition to obesity.
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Contributions of incidence and persistence to the prevalence of childhood obesity during the emerging epidemic in Denmark.
PLoS ONE
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Prevalence of obesity is the result of preceding incidence of newly developed obesity and persistence of obesity. We investigated whether increasing incidence and/or persistence during childhood drove the prevalence of childhood obesity during the emerging epidemic.
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Invited commentary: How early in life does the risk of obesity originate?
Am. J. Epidemiol.
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Mothers and fathers influence the risk of obesity in their children through genetic, environmental, and behavioral factors. Unique to the mother, however, is the intrauterine environment in which the fetus develops, and it is during this time in the uterus that the risk of later obesity in the child may develop. In this issue of the Journal, Fleten et al. (Am J Epidemiol. 2012;176(2):83-92) investigate whether the intrauterine environment plays a role in the development of adiposity by comparing the association between maternal prepregnancy body mass index (BMI; measured as weight in kilograms divided by height in meters squared) and offspring BMI at 3 years of age with the paternal-offspring association at the same age in the Norwegian Mother and Child Cohort Study. In that large study of stable, relatively healthy and well-educated families, significant differences in maternal-offspring and paternal-offspring BMI associations were not identified. These findings are interpreted as indicating that the influence on the childs BMI of the intrauterine environment is less important than that of genetics and shared environment. Results from that study suggest that further consideration should be given to the specificity of the fetal overnutrition hypothesis in terms of which aspects of the intrauterine environment may influence offspring adiposity and when across the life course these effects may manifest themselves.
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Hyperbranched polyglycerols as trimodal imaging agents: design, biocompatibility, and tumor uptake.
Bioconjug. Chem.
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Combining various imaging modalities often leads to complementary information and synergistic advantages. A trimodal long-circulating imaging agent tagged with radioactive, magnetic resonance, and fluorescence markers is able to combine the high sensitivity of SPECT with the high resolution of MRI over hours and days. The fluorescence marker helps to confirm the in vivo imaging information at the microscopic level, in the context of the tumor microenvironment. To make a trimodal long-circulating probe, high-molecular-weight hyperbranched polyglycerols (HPG) were modified with a suitable ligand for (111)In radiolabeling and Gd coordination, and additionally tagged with a fluorescent dye. The resulting radiopharmaceutical and contrast agent was nontoxic and hemocompatible. Measured radioactively, its total tumor uptake increased from 2.6% at 24 h to 7.3% at 72 h, which is twice the increase expected due to tumor growth in this time period. Both in vivo MRI and subsequent histological analyses of the same tumors confirmed maximum HPG accumulation at 3 days post injection. Furthermore, Gd-derivatized HPG has an excellent contrast enhancement on T1-weighted MRI at 10× lower molar concentrations than commercially available Galbumin. HPG derivatized with gadolinium, radioactivity, and fluorescence are thus long-circulating macromolecules with great potential for imaging of healthy and leaky blood vessels using overlapping multimodal approaches and for the passive targeting of tumors.
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Growth in height in childhood and risk of coronary heart disease in adult men and women.
PLoS ONE
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Adult height is inversely associated with the risk of coronary heart disease (CHD), but it is still unknown which phase of the human growth period is critical for the formation of this association. We investigated the association between growth in height from 7 to 13 years of age and the risk of CHD in adulthood.
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Evaluation of Patient Satisfaction with Diabetes Management Provided by Clinical Pharmacists in the Patient-Centered Medical Home.
Patient
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The patient-centered medical home (PCMH) model is a multidisciplinary, team-based approach to healthcare that focuses on actively involving the patient in clinical decision making. Multiple studies have demonstrated improved clinical outcomes from utilizing clinical pharmacists in the primary care setting, particularly in management of diabetes. No study has evaluated patient satisfaction with pharmacist in the PCMH model. Our objective was to evaluate patient satisfaction of care received in pharmacist-managed primary care clinics among patients with diabetes mellitus within the PCMH.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.